Good in small doses: Damaging chemicals may benefit brain, too

Reactive chemicals that cause damaging oxidation to the nervous system may actually improve sensory function at low doses, researchers at the University of Michigan Life Sciences Institute and collaborators at Huazhong University of Science and Technology in China have found.

The progression of neurodegenerative diseases such as Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis is associated with oxidative stress — damage to cells caused by a group of chemicals produced by the body known as reactive oxygen species.

The new findings, published today in Nature Communications, uncover a beneficial effect of these chemicals on neurons — opening a new entry point for investigating their multifaceted role in nervous system health and disease.

The researchers exposed millimeter-long roundworms — a model organism with a well-mapped nervous system — to hydrogen peroxide and examined their behavioral responses to sensory cues. Higher concentrations suppressed the worms’ ability to avoid a drop of glycerol in its path, while very low doses led to better-than-normal responses.

Similar effects were seen in other sensory behaviors, such as the worms’ attraction to a pleasant smell.

“Our research reveals an unexpected complexity in the effects of oxidative stressors on the nervous system,” says study co-senior author Shawn Xu, Ph.D., a faculty member at the LSI, where his lab is located. “Since the signaling pathway that’s involved is evolutionarily conserved, the results raise the intriguing possibility that these chemicals may play a similar role in regulating brain function in complex organisms.”

Reactive oxygen species are produced by the body as a natural response to certain conditions, and beneficial effects are already being studied in other contexts, such as stress resistance.

The new findings were validated by showing that reducing naturally occurring levels of hydrogen peroxide with antioxidants also suppressed the worms’ avoidance behavior.

“These reactive oxygen species are associated with stress responses to harsh environments, so it makes sense that small amounts of these chemicals might sensitize sensory neurons and help the worms escape,” says Xu, who is also a professor in the Department of Molecular and Integrative Physiology at the U-M Medical School.

Additional authors: Guang Li, Jianke Gong and Haoyun Lei of U-M and Huazhong University of Science and Technology; Jianfeng Liu of Huazhong University of Science and Technology.

Funding: National Natural Science Foundation of China, the Ministry of Education of China, the Ministry of Science and Technology of China, and the U.S. National Institute of General Medical Sciences